Kevin-Hall.pdf

Why is i s it s o Hard Hard to t o Lose Lo se Weight Weight and Kee K eep p it Off? Kevin D. Hall, Hall, Ph.D. Nation Na tion al Institut e of Diabetes & Digestive & Kid ney Disea Diseases ses Nation Na tion al Institutes of He Health alth

@KevinH_PhD July 20, 2018

Calories In & Out are NOT Independent Calories Out

Calories In

Feedback Regulation of Body Weight

Calories Out

Leptin, etc.

Calories In

Feedback Regulation of Body Weight

Calories Out

Leptin, etc.

Calories In

Mathematical Modeling of Metabolism dG  C

ˆ

CI

=

dt

3 M FFA FI M TG

=

dt

PI

=

dt

FFM

− G 3P − CarbOx

+

d

DNL − KU excr

−

(1 −  ) KTG − FatOx k

(

CI  G Ginit

(G

Ginit

)

d

− GNG

BM

+

ECP + LCM

K DNL

 G  =D   G  ˆ

G

2

 F DF = D F   F Keys 

init

= BM +

ECF

+

ECP + ICW

+

P + G + ICS

= BM +

ECF

+

ECP + ICW

+

P(1 + hP ) + G (1 + hG ) + ICS

=

1



Na

d E CF dt =

TEF

+



ˆ

(  Na

diet

(

)

(

−  Na ECF − ECFinit −  CI 1− CI CI b

dt

(

i

PAE

+

EI b EI b

) −T , ) − T ,

 P   PKeys

ˆ

)



M G



M TG

 C 

TG

GNGP = GNGP 

3

)

  

LPA

S L



− Ldiet

  +   =   − 1 +     init

i nit

  CI   PI    − C   + ( P +  )    CI b   PIb   

  DF DF    PI  G  =  K DF  AK   exp  −kP  exp  −kG  PIb  Ginit     K K + DF DF     0, if KTG  K  KTGthresh     =   K KU max ( KTG  K − KTGthresh )  , else   − KTG KTG ( ) max thresh   ˆ

KTG

(

)



ˆ

dP dt

+ F DF + F

dF dt

KU excr

dG

+ G DG +G

dt

if EI  EI b   else

f C =

 

dM i dFFM

G

F

F

RMR

 FFM =  FFM 1 + (1 −  ) T 

(

S

C

) ) +  ECF

)



(

K L L + MAX 0, F FKeys −1

  M  = FI  + D   M 

GNGF

=  BW BW − BWinit − ECF

  (  EI =  1  2 (  EI

=   i

dt

   Ldiet + LPA  

K LS L 1 + ( AL − BL )  exp ( −kL CI CIb ) + BL 

=

ˆ

+ N Nexcr + (P +  P ) DP + P dT

dLdiet

L

+(1 −  d ) DNL + (1 −  g )(GNGF + GNGP ) + (1 −  K ) KTG

ˆ

DG

d





 FFM

d

ProtOx

−

P

RMR = Ec +  B M B +  FFM  FFM − M B − G 1 + hg − ( ECF − ECFinit )  +  F F

 T

+

)

ECF

dt

TEE

F

+

=

dECF

 BW

+ GNG

ˆ

dP  P

DNL + GNGP

DNL =

dF  F

−

 P   PI  +        PI b    PKeys 

DP = DP 

f F = CarbOx = GNG f

+

GNGp

−

FatOx = KetOx + f F  TEE

G3 P + fC  TEE f P =

wG ( DG DG ) + wC MAX 0, (1 + SC CI CI b ) G ( Gmin + G) ˆ

Z

(

wF DF DF ˆ

)

Z



 (

)

wP MAX 0, (1 + Psig ) + DP DP S A exp ( − k A (  +  ) ( b + b ) ) ˆ

Z

Mathematical Modeling of Metabolism Baseline Demographics & Anthropometrics Physical Activity Food Intake

Mathematical Model of Human Metabolism

Body Weight Body Fat

Corrected Weight Loss Projections

Dynamic Model

3500 kcal per lb rule

BWplanner.niddk.nih.gov

The Biggest Loser Competition

Biggest Loser Body Weight and Fat Loss Isolated on Ranch

20 ) g k (

At Home

0

e g -20 n a h C-40 s s a M-60

Fat Mass Body Weight

-80 -4

0

4

8

12

16

Time (weeks)

20

24

28

Mean ± SD

32

Biggest Loser Energy Balance Dynamics 6000

Total Energy Expenditure

) 5000 d / l a c 4000 k ( e t a 3000 R y g r 2000 e n E 1000

0 -4

0

4

8

12

16

20

24

28

Time (weeks) Mean ± SD

32




Exercise

0 -4

0

4

8

12

16

20

24

28


32




Resting Metabolic Rate Exercise

0 -4

0

4

8

12

16

20

24

28


32

Metabolic Rate before the Biggest Loser 4000

) d3500 / l a c k ( e t a3000 R c i l o b a t 2500 e M g n i t s e2000 R

R2 =0.85

1500 40

60

80

Fat-Free Mass (kg)

100

120

Metabolic Rate after the Biggest Loser 4000

) d3500 / l a c k ( e t a3000 R c i l o b a t 2500 e M g n i t s e2000 R

Metabolic Adaptation

1500 40

60

80

Fat-Free Mass (kg)

100

120

Body Weight Regain p=0.0002

40

*

20

) g k ( 0 e g n -20 a h C t -40 h g i e -60 W y d -80 o B

*

-100 -120

30 weeks

6 years *p <0.05 vs. baseline

What Determines Weight Regain? 200

P = 0.003

Physical Activity

s r a 150 e y 6 r e 100 t f a e g n 50 a h C 0 %

Energy Intake

P = 0.83

-50 > 13% Weight Loss

< 13% Weight Loss

(-24.9% ± 3.8%)

(+1.1% ± 4.0%)

Weight Regain & Energy Intake

r = -0.15 p = 0.61

Weight Regain & Physical Activity r = -0.82 p = 0.0003

Resting Metabolic Rate Remained Low p=0.35 0

*-200 ) -400 y a d -600 / l a -800 c k ( e -1000 g n -1200 a h C -1400 R M-1600 R

*

*

*

-1800 -2000

30 weeks


Metabolic Adaptation Persisted p=0.0075 100

) 0 d / l a -100 c k ( -200 n o i t -300 a t p -400 a d -500 A c i -600 l o b -700 a t e -800 M

*

*

-900

30 weeks


Weight Regain & Metabolic Adaptation n o i t a t p a d A ) c i d / l l o a c b k a ( t e M k w 0 3

200

r=-0.1 p=0.75

0 -200 -400 -600 -800

-1000 -50

0

50

100

% Weight Gained at 6 years

150

Weight Regain & Metabolic Adaptation n o i t a t p a d ) A d c l i / l a c o k b ( a t e M r y 6

200 0

r=0.59 p=0.025

-200 -400 -600 -800 -1000 -50

0

50

100

% Weight Gained at 6 years

150

Spring Model of Metabolic Adaptation





Feedback Control of Appetite

?? Calories Out

~90 g/d glucose

Leptin, etc.

Calories In

Weight Changes during SGLT2 Inhibition 0

) g-1 k ( t h g i -2 e W y-3 d o B Δ-4

N=153 adults with Obesity & Type 2 diabetes treated with canagliflozin

-5 0

6

12

18

24

30

Time (weeks)

36

42

48

54

Intake Changes during SGLT2 Inhibition 500

) d / l 400 a c k ( 300 e k a t 200 n I y 100 g r e n 0 E Δ

~100 kcal/d per kg BW loss

-100 0

6

12

18

24

30

Time (weeks)

36

42

48

54

Feedback Regulation of Body Weight ~20-30 kcal/d per kg Calories Out

Leptin, etc.

~100 kcal/d per kg Calories In

Typical Weight Loss with Lifestyle Change 97

) 95 g k ( t 93 h g i e91 W y d89 o B87

N=211 clients of Weight Watchers

85 0

3

6

9

12

Months

15

18

21

24

Mean ± SE

Corresponding Calorie Balance Dynamics 2700

e r u t i d 2500 n e ) p d x / E l 2300 a c d k n ( a e k 2100 a t n I

Calorie Expenditure Exponential decay of diet adherence!

Calorie Intake

1900

0

3

6

9

12

Months

15

18

21

24

Interpreting Lifestyle Weight Loss 3500


Calorie Expenditure Calorie Intake

1900

0

3

6

9

12

Months

15

18

21

24



Increased Appetite Perceived Effort Calorie Expenditure Calorie Intake

1900

0

3

6

9

12

Months

15

18

21

24


Perceived Effort

600 400

200 d / l 0 a c k-200 -400

Calorie Intake Change

-600 -800 0

3

6

9

12

Months

15

18

21

24

Summary •

•

The body resists weight loss and promotes weight regain via slowing metabolism and increased appetite Long-term maintenance of lost weight requires ongoing support and persistent effort –

–

–

Increased physical activity may be especially beneficial for maintaining lost weight, in addition to overall health benefits Reengineering your local environment may help facilitate maintenance of lost weight Drugs may help, but they need to be sustained to have lasting effects

Kevin-Hall.pdf

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